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GSE14662
Mus musculus
5 Downloadable Samples
Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
Tumors express a wide variety of both mutated and non-mutated antigens. Whether these tumor antigens are broadly recognized as self or foreign by the immune system is currently unclear. Using an autochthonous prostate cancer model in which hemagglutinin (HA) is specifically expressed in the tumor (ProHA x TRAMP mice), as well as an analogous model wherein HA is expressed in normal tissues as a model self-antigen (C3HAHigh), we examined the transcriptional profile of CD4 T cells undergoing antigen-specific division. Consistent with our previous data, transfer of antigen-specific CD4 T cells into C3HAHigh resulted in a functionally inactivated CD4 T cell profile. Conversely, adoptive transfer of an identical CD4 T cell population into ProHA x TRAMP resulted in the induction of a regulatory phenotype (Treg) both at the transcriptional and functional level. Interestingly, this Treg skewing was a property of even early-stage tumors, suggesting Treg induction as an important tolerance mechanism during tumor development.
Publication Title
No associated publication
Sample Metadata Fields
No sample metadata fields
View Samples- Homo sapiens
- 2 Downloadable Samples
- Affymetrix Human Gene 2.0 ST Array (hugene20st)
Description
Evaluation of the genome wide impact of PARPi gene expression programs
Publication Title
PARP-1 regulates DNA repair factor availability.
Sample Metadata Fields
Specimen part, Cell line
View Samples- Mus musculus
- 8 Downloadable Samples
- Affymetrix Mouse Genome 430 2.0 Array (mouse4302)
Description
The RB and p53 tumor suppressor pathways regulate the transcription of genes involved in cell cycle progression, DNA replication, DNA repair, and apoptosis. These tumor suppressors are critical modulators of the response to genotoxic damage and both pathways are frequently inactivated in human cancers.
Publication Title
No associated publication
Sample Metadata Fields
Specimen part
View Samples- Homo sapiens
- 47 Downloadable Samples
- Affymetrix Human Genome U133A Array (hgu133a)
Description
K562 cell line mock treated or for 24 hours with one micromolar imatinib.
Publication Title
No associated publication
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus, Homo sapiens
- 56 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Constitutive MET signaling promotes invasiveness in primary and recurrent GBM; however, current MET-targeting strategies lack of effective biomarkers for selecting suitable patients for treatment. Here, we identified a predictive signature potentially valuable for indicating vulnerability to MET-targeted therapy in GBM. The use of both human and mouse gene expression microarrays showed that MET inhibitors regulate tumor (human) and host (mouse) cells within the tumor via distinct molecular processes, but overall they impede tumor growth by inhibiting cell cycle progression. Notably, GBM tumors with EGFRamp that showed resistance to erlotinib treatment also showed activation of the MET pathway, suggesting that a combination of EGFR and MET inhibitors may overcome or prevent such resistance in patients with EGFRamp GBM.
Publication Title
No associated publication
Sample Metadata Fields
Specimen part, Disease, Disease stage, Cell line
View Samples- Homo sapiens
- 9 Downloadable Samples
- Affymetrix Human Genome U133 Plus 2.0 Array (hgu133plus2)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Large-scale hypomethylated blocks associated with Epstein-Barr virus-induced B-cell immortalization.
Sample Metadata Fields
Specimen part, Time
View Samples- Mus musculus
- 23 Downloadable Samples
- Affymetrix Mouse Gene 2.0 ST Array (mogene20st)
Description
Human mucosal surfaces contain a wide range of microorganisms. The biological effects of these organisms are largely unknown. Large-scale metagenomic sequencing is emerging as a method to identify novel microbes. Unexpectedly, we identified DNA sequences homologous to virus ATCV-1, an algal virus not previously known to infect humans, in oropharyngeal samples obtained from healthy adults. The presence of ATCV-1 was associated with a modest but measurable decrease in cognitive functioning. A relationship between ATCV-1 and cognitive functioning was confirmed in a mouse model, which also indicated that exposure to ATCV-1 resulted in changes in gene expression within the brain. Our study indicates that viruses in the environment not thought to infect humans can have biological effects.
Publication Title
Chlorovirus ATCV-1 is part of the human oropharyngeal virome and is associated with changes in cognitive functions in humans and mice.
Sample Metadata Fields
Treatment
View Samples- Rattus norvegicus
- 20 Downloadable Samples
- Affymetrix Rat Clariom S Assay (clariomsrat)
Description
Mania is a serious neuropsychiatric condition associated with significant morbidity and mortality. Previous studies have suggested that environmental exposures can contribute to mania pathogenesis. We measured dietary exposures in a cohort of individuals with mania and other psychiatric disorders as well as in control individual without a psychiatric disorder. We found that a history of eating nitrated dry cured meat, but not other meat or fish products, was strongly and independently associated with current mania (adjusted odds ratio 3.49, 95% confidence interval (CI) 2.24-5.45, p<8.97x 10-8). Lower odds of association were found between eating nitrated dry cured meat and other psychiatric disorders. We further found that the feeding of meat preparations with added nitrate to rats resulted in alterations in behavior and changes in intestinal microbiota. Rats fed diets with added nitrate also showed alterations of brain pathways dysregulated in mania. These findings may lead to new methods for preventing mania and for developing novel therapeutic interventions
Publication Title
Nitrated meat products are associated with mania in humans and altered behavior and brain gene expression in rats.
Sample Metadata Fields
Sex, Specimen part
View Samples- Homo sapiens
- 16 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
The size of lentiviral DNA reservoirs reflects effectiveness of immune responses against lentiviruses. So far, abundant information has been gathered on the control of HIV-1 replication. Understanding of innate mechanisms contributing to containment of HIV-DNA reservoir, however, are only partly clarified and are relevant to guide interventions for reservoir containment or eradication. We studied the contribution of Natural Killer (NK) cell functional features in HIV patients either controlling replication either spontaneously (HIC) or after progression and antiretroviral treatment (PP). An inverse correlation between HIV-DNA copy numbers (either total or integrated) in circulating CD4+ cells and NK cell function were observed. Induced IFN-gamma production and NKp46/NKp30 activating receptor-induced expression correlated inversely with reservoir size. The correlation was present not only when considering a homogeneous cohort of HIC patients, but also when PP patients were included in the analysis. Adaptive (NKG2C + CD57 + ) NK cell features were not associated with reservoir size. However a distinct set of 370 differentially expressed transcripts was found to underlie functional differences in NK cells controlling HIV-DNA reservoir size. In proof-of-principle in vitro experiments of CD4+ cell infection with HIV-1, purified NK cells with the above functional/transcriptional features displayed a 10- and 30-fold higher ability to control HIV replication and DNA burden in vitro, respectively, compared to other NK cells. Thus, NK cells with a specific functional and transcriptional signature contribute to control of HIV reservoir in CD4+ cells. Their selection, expansion and/or adoptive transfer may support strategies to eradicate HIV-1 infection or to safely deescalate antiretroviral treatment.
Publication Title
No associated publication
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples- Mus musculus
- 13 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Kabuki syndrome is a Mendelian intellectual disability syndrome caused by mutations in either of two genes (KMT2D and KDM6A) involved in chromatin accessibility. We previously showed that an agent that promotes chromatin opening, the histone deacetylase inhibitor (HDACi) AR-42, ameliorates the deficiency of adult neurogenesis in the granule cell layer of the dentate gyrus, and rescues hippocampal memory defects in a mouse model of Kabuki syndrome (Kmt2d+/Geo). Unlike a drug, a dietary intervention could be quickly transitioned to the clinic. Therefore, we have explored whether treatment with a ketogenic diet could lead to a similar rescue through increased amounts of beta-hydroxybutyrate, an endogenous HDACi. Here, we report that a ketogenic diet in Kmt2d+/Geo mice modulates H3ac and H3K4me3 in the granular cell layer, with concomitant rescue of both the neurogenesis defect and hippocampal memory abnormalities seen in Kmt2d+/Geo mice; similar effects on neurogenesis were observed upon exogenous administration of beta-hydroxybutyrate. These data suggests that dietary modulation of epigenetic modifications through elevation of beta-hydroxybutyrate may provide a feasible strategy to treat the intellectual disability seen in Kabuki syndrome and related disorders.
Publication Title
No associated publication
Sample Metadata Fields
Sex, Specimen part
View Samples